The objectives of this proposal are to determine the precise relationship between the genetic locus coding for the enzyme Esterase D and the RB-l locus, defined by an interstitial deletion of chromosome 13, on human chromosome 13 by quantitative assays of Esterase D and karyotype analysis of members of families with multiple generations of retinoblastoma patients. To determine whether the quantitation of Esterase D is a useful tool in searching for deletions of chromosome 13 not visible during karyotype analysis, and to apply this to individuals with retinoblastoma in the absence of an obvious deletion. To search for evidence for the involvement of more than one genetic locus in the development of retinoblastoma by linkage analysis between RB-l and a large battery of genetic markers as a test of the multi-hit hypothesis for childhood cancer.